1. Field of the Invention
At least one embodiment of the invention relates to a cardiac stimulator comprising at least one stimulation unit, at least three stimulation electrode poles and at least one electrode lead. The at least one stimulation unit is connected or to be connected to the at least three stimulation electrode poles via the at least one electrode lead and is configured to deliver subthreshold stimulation pulses for a cardiac contractility modulation (CCM) therapy via the at least two stimulation electrode poles.
2. Description of the Related Art
Implantable cardiac stimulators in the form of cardiac pacemakers or cardioverters/defibrillators are common in the field of art. Such cardiac stimulators are generally connected to electrode leads, which have stimulation electrodes, and optionally include additional defibrillation electrodes, in a ventricle of a heart or in the direct vicinity thereof. Via a stimulation electrode, a cardiac pacemaker can deliver an electrical stimulation pulse to the muscle tissue of a ventricle, so as to evoke a stimulated contraction of the ventricle, provided that the stimulation pulse is sufficiently intense and the heart muscle tissue (myocardium) is not presently in a refractory phase. Within the scope of this description, such a stimulated contraction of a ventricle is referred to as a stimulated event, and a stimulation pulse that has sufficient intensity to evoke a stimulated contraction of a ventricle is referred to as “suprathreshold”. When a natural contraction of the ventricle occurs, it is referred to as an intrinsic activity, or as a natural or intrinsic event, within the scope of this description. A contraction of the right atrium of a heart, for example, is referred to as an atrial event, which can be a natural atrial event, for example, or—in the case of an atrial cardiac pacemaker—a stimulated atrial event. Similarly, a distinction can be made between natural (intrinsic) and stimulated left-ventricular and right-ventricular events.
Starting from the excitation site, a local excitation of the myocardium spreads in the myocardium by way of stimulus conduction and results in a depolarization of the muscle cells, and hence in a contraction of the myocardium. After a short time, a repolarization of the muscle cells occurs, and hence a relaxation of the myocardium. During the depolarization phase, the myocardium cells are not receptive to excitation, as they are refractory. The period is referred to as a refractory period. Electrical potentials accompanying the depolarization and repolarization can be detected and the temporal curves thereof—an electrocardiogram—can be evaluated.
An electrocardiogram shows action potentials that reflect a depolarization of the myocardial cells and accompany a contraction of the ventricle reflectled in a Q-wave, while the repolarization of the myocardial cells accompanying the relaxation of the myocardium is reflected in a T-wave.
In healthy people, the respective cardiac rhythm is determined by a sinoatrial node controlled by the autonomic nervous system. By way of stimulus conduction, the sinoatrial node excites the right atrium of a human heart, and an AV node excites the (right) ventricle of the heart. A natural heart rhythm originating from the sinoatrial node is therefore also referred to as a sinus rhythm and results in respective natural contractions of the respective ventricle, that can be detected as natural (intrinsic) events.
Such natural (intrinsic) events are detected by measuring the electrical potentials of the myocardium of the respective ventricle using sensing electrodes, that are part of a corresponding electrode lead. The sensing electrodes can also be the stimulation electrodes and be used alternately as stimulation and as sensing electrodes. Sensing—for example the perception of intrinsic events—is typically carried out by a sensing electrode pair, which is formed by two adjoining electrodes, more specifically a tip electrode and a ring electrode, of which the tip electrode is also used as the stimulation electrode. In this way, a bipolar measurement of an intracardiac electrocardiogram (IEGM) is obtained. The sensing and the stimulation in the ventricle take place with the aid of a ventricular electrode lead and the stimulation and the sensing in the atrium (in the right atrium) take place with an atrial electrode lead, that are connected separately to the respective cardiac stimulator. Additionally, a left-ventricular electrode lead may be provided, which typically projects over the coronary sinus and a lateral vein branching off the coronary sinus, and into the vicinity of the left ventricle. In the vicinity of the left ventricle, the left-ventricular electrode lead can comprise a small-surface-area stimulation and/or sensing electrode.
With respect to the terms used herein, it shall be pointed out that within the scope of this text the terms stimulation electrode or sensing electrode refer to a respective electrode pole on an electrode lead, wherein stimulation pulses are delivered or electrical potential is taken up. It is also be pointed out that it is also customary to refer to an electrode lead used for stimulation as a “stimulation electrode”.
During operation of the cardiac stimulator, the sensing electrodes are connected to corresponding sensing units, which are configured to evaluate a respective electrocardiogram recorded using a sensing electrode (or a sensing electrode pair) and in particular to detect intrinsic atrial or ventricular events; natural atrial or ventricular contractions. This is done, for example, by a threshold comparison, wherein an intrinsic event is detected when a respective intracardiac electrocardiogram exceeds a suitably predefined threshold.
The respective intrinsic atrial heart rate (atrial frequency) or ventricular heart rate (ventricular frequency) can be derived from the frequency at which the atrial or ventricular events follow each other, and tachycardia, for example, can thus be detected.
In typical demand pacemakers, the detection of natural events is also used to suppress (inhibit) the delivery of stimulation pulses to a corresponding ventricle, if the natural event is detected during a time window prior to the planned delivery of a stimulation pulse to the ventricle. In rate-adaptive cardiac pacemakers, the time at which a respective stimulation pulse is delivered is scheduled as a function of a respective stimulation rate, corresponding to the physiological need of a patient. For example, it is greater with greater exertion. For this purpose, a cardiac stimulator can be equipped with one or more activity sensors, which can be a CLS sensor, for example, which will be described in more detail hereafter.
The natural effect of the autonomic nervous system on the heart rate, which is reproduced by a rate-adaptive cardiac stimulator, is referred to a chronotropy.
In addition to the chronotropy, the cardiac performance is also determined by the contractility of the heart, referred to as inotropy.
To determine the contractility of a heart, it is typical to arrange an impedance or conductivity measuring unit in a housing of a cardiac stimulator (for example an implantable cardiac pacemaker). The unit is configured to generate a unipolar or bipolar impedance or conductivity curve signal. For this purpose, several impedance or conductivity values are measured, or a corresponding impedance or conductivity curve is measured, during at least one cardiac cycle. This is done either in a unipolar manner by measuring between a neutral electrode and a measuring electrode, or between two measuring electrodes. Moreover, an evaluation unit is arranged in the housing, to evaluate the impedance or conductivity curve and derive a contractility value from the impedance or conductivity curve. Electrotherapy devices, which are able to determine the contractility of a heart, provide the option to adapt a therapy to be delivered by the electrotherapy device to the respective contractility state of the heart of the patent.
As indicated above, the contractility describes the inotropic state of a heart. The contractility influences the force and speed of a myocardial contraction. Contractility is controlled by three mechanisms:                direct control by the autonomic nervous system (ANS),        the so-called Frank-Starling mechanism and        the so-called Bowditch effect (force-heart rate coupling).        
The primary mechanism, controlling the circulatory system regulation through the autonomic nervous system, increases the contractility and the heart rate when an increased metabolic need exists, for example during physical exertion, so as to ensure suitable blood supply. In healthy people, the inotropy of the heart thus causes a rise in the contractility due to increased physiological demand.
In patients with chronic heart failure (HF), the myocardial contractility decreases to a low level and the interventricular synchronization worsens. This is accompanied by a low ejection fraction (EF) as well as by a low quality of life and high mortality. HF is common among the population. Recently, HF patients are treated with resynchronization therapy devices, for example 3-chamber cardiac pacemakers or defibrillators. The objective of such a therapy is to synchronize the two ventricles of a heart by way of biventricular stimulation so as to improve the time response of the ventricles and consequently cardiac performance. Such a therapy is also referred to as cardiac resynchronization therapy (CRT). Cardiac resynchronization therapy (CRT) is sufficiently known and is provided, for example, by BIOTRONIK CRT-D implants (Lumax HF-T).
Cardiac resynchronization therapy (CRT) is a special form of the more general cardiac rhythm management (CCM), which also includes, for example, simple stimulation of only one ventricle to treat bradycardia. A CRM stimulator can therefore also be a single-chamber cardiac pacemaker.
Because the contractility of the heart can be controlled physiologically by the autonomic nervous system, the detection of the contractility can also be utilized to adjust a physiologically adequate stimulation rate in rate-adaptive cardiac pacemakers. This type of stimulation rate control, as addressed above, is also known as closed loop stimulation (CLS).
For CLS, the intracardiac impedance curve after start of the ventricle contraction is measured. This measurement is carried out both for intrinsic and for stimulated events. There is a direct dependency between the right-ventricular impedance curve and the contraction dynamics. The contraction dynamics, in turn, is a parameter for the stimulation of the heart by the sympathetic nervous system.
Closed loop stimulation is, as mentioned above, the control of the stimulation rate with a rate-adaptive cardiac pacemaker.
Cardiac contractility modulation (CCM) therapy mainly used to increase the contractility of a ventricle.
The company Impulse Dynamics, for example, offers an OPTIMIZER system for CCM therapy. This system comprises a stimulation pulse generator, connected to three electrodes, one of which one is arranged during operation in the atrium and on the septum of the right ventricle of a patient. The principle of the therapy is based on a delivery of biphasic stimulation pulses having amplitudes of 7V to 10V and a total pulse duration of ˜20 ms in the absolute refractory period of the ventricle with the goal of increasing contractility. The therapy is delivered for certain periods of time of the day (for example, alternately 1 hour on, 1 hour off).
The principle of cardiac contractility modulation therapy is described, amongst others, in U.S. Pat. No. 6,317,631 B1.
The effect of the CCRM therapy is based—according to present assumptions—on a modification of the cellular calcium ion exchange and thus results in an increased contraction force, which could also result in a therapeutic benefit with any existing atrial fibrillation. While this has not yet been clinically proven, it is understood pathophysiologically.
Patent Application Publication Nos. U.S. 2010/0069977 A1, U.S. 2010/0069980 A1, U.S. 2010/0069984 A1 and U.S. 2010/0069985 A1 describe methods for delivering CCM stimulation as needed. They describe, in general terms, the use of physiological sensors, kidney or heart function sensors, electrolyte sensors, serum sensors (for example creatinine), neurosensors (vagus, sympathetic nervous system), adverse event detectors, worsening heart failure sensors, MRI sensors, activity sensors, sleep apnea sensors, ischemia sensors, sensors for metabolic needs, and infarction sensors, as well as heart rhythm-dependent CCM controllers. The aforementioned prior art also describes the disabling of the CCM therapy when atrial fibrillation or atrial arrhythmia is detected (e.g. see U.S. 2010/0069977, FIG. 20A and paragraph [0332]). Similarly, the following description addresses, in very general terms, the possible combination of CCM with other stimulation and electrotherapy forms such as CRT, ICD and neurostimulation. Patent Application Publication Nos. U.S. 2010/0069977 A1, U.S. 2010/0069980 A1, U.S. 2010/0069984 A1 and U.S. 2010/0069985 A1 describe the disabling of the CCM therapy when atrial fibrillation or atrial arrhythmia is detected, however the reason for CCM disabling is not addressed in detail.
Patent Application Publication Nos. U.S. 2010/0069977 A1, U.S. 2010/0069980 A1, U.S. 2010/0069984 A1 and U.S. 2010/0069985 A1 also describe the possible combination of CCM and CRT stimulation in a device.
CCM stimulation pulses are normally delivered in the absolute refractory period of a respective ventricle. These pulses can thus be prevented from inducing arrhythmia.
The CCM system presently available on the market (Optimizer III by Impulse Dynamics) synchronizes the CCM pulses by sensing of septal excitation using a local CCM electrode.
The inventor has recognized the following disadvantages of known CCM stimulators:
With the aforementioned method of CCM synchronization, sensing errors can cause the CCM pulses to be delivered even outside the absolute refractory period. This can have a proarrhythmic effect and induce ventricular tachycardia or ventricular fibrillation.
This risk is increased especially when using CCM stimulation together with additional stimulators, such as a biventricular pacemaker or defibrillator, because delivery of subthreshold stimuli can be sensed via the CCM system, which could trigger delivery of a CCM pulse.
A further disadvantage of the CCM therapy consists in the necessity to implant two additional stimulation electrodes at the ventricular septum. With the simultaneous use of an ICD or CRT-D, the number of implanted electrodes becomes very large.
Contrary to other CRM stimulators, no stimulation success control is known for the present CCM system. The therapy parameters are established empirically and at best adapted to the clinical long-term progression. Device-internal optimization of the therapy does not exist as of yet.
Based on the disadvantages of the prior art that the inventor has recognized, it is the objective of at least one embodiment of the invention to create an improved cardiac stimulator for cardiac contractility modulation therapy.